课题基金基金详情
CircRNA_0013372-miR-21-Smad7轴在糖尿病肾病中的作用及调控机制
结题报告
批准号:
81760147
项目类别:
地区科学基金项目
资助金额:
34.0 万元
负责人:
王金羊
依托单位:
学科分类:
H0708.糖尿病
结题年份:
2021
批准年份:
2017
项目状态:
已结题
项目参与者:
魏素虹、安思芹、冯婧、吴晓媛、杨译、张广润、李潇、王百灵
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中文摘要
糖尿病肾病(DN)的发病机制未完全阐明,肾小管上皮细胞转分化(EMT)与DN密切相关。circRNA为一种新的调控miRNA功能的RNA分子,广泛参与了多种疾病的发病过程。我们前期研究发现: circRNA_0013372在DN肾脏组织中的表达降低,而miR-21表达升高;miR-21可能是circRNA_0013372的潜在靶点;miR-21过表达能下调Smad7。故推测circRNA_0013372可能通过下调miR-21参与EMT。因此,本课题针对DN发病的中心环节—EMT,以miR-21-Smad为切入点,以circRNA_0013372为研究靶点。采用FISH、RT-PCR、WB、细胞转染、荧光素酶报告基因,进一步阐明circRNA_0013372-miR-21-Smad7轴在EMT发病机制,为将来研发以circRNA为靶点的防治DN药物提供理论依据。
英文摘要
The pathogenesis ofdiabetic nephropathy(DN) has not been fully elucidated.Epithelial-to-mesenchymal transition (EMT) is closely related to diabetic nephropathy (DN). CircRNA was as a new RNA molecules with regulation of miRNA function, widely involved in the disease process of many diseases. Our preliminary experiments showed that there was the decrease of circRNA_0013372 expression and the increase of miR-21 in kidney tissues with DN. miR-2 1may be circRNA_0013372 potential targets. miR-21 overexpression decreased smad7 expression. Hereby, we speculated that circRNA_0013372 may be involved in the EMT by downregulating miR-21. In this study, EMT was as a center-link of DN, miR-21-smad7 was as the key breakthrough point, circRNA_0013372 was as a research targets. FISH, RT-PCR, cell transfection, luciferase reporter gene assays, WB and confocal microscope were used, respectively. This study will further elucidate the pathogenesis of circRNA_0013372-miR-21-Smad7 axis in the EMT,and provide theoretical basis for the prevention and treatment of DN with circRNA-targets drugs in the future.
糖尿病肾病(diabetic nephropathy,DN)是糖尿病最主要的微血管并发症之一,但其发病机制尚未完全阐明。circRNA_0013372作为一种新型调控miRNA功能的RNA分子,影响 miRNAs下游靶基因的表达发挥重要的调控作用。本课题采用KK-Ay糖尿病肾病模型和肾小管上皮细胞模型,针对DN发病的中心环节——肾小管上皮细胞转分化(EMT),以转分化和纤维化基因调控网络中的关键成分miR-21和TGF-β1/Smad为切入点,以circRNA_0013372为研究靶点。采用基因重组circRNA过表达、siRNA、原位杂交、RT-PCR、Western-Blot,细胞转染、荧光素酶报告基因检测及激光共聚焦等技术,从整体、细胞、分子水平三个层次结果阐明:(1)circRNA_0013372-miR-21-Smad7轴在糖尿病肾病EMT的发病机制中的作用。(2)circRNA_0013372能成为治疗DN新的作用靶点之一。该研究成果将为DN的发展机制提供理论依据,并为为将来开发以circRNA为靶点治疗DN药物提供理论依据。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Angiotensin II receptor blocker valsartan ameliorates cardiac fibrosis partly by inhibiting miR-21 expression in diabetic nephropathy mice
血管紧张素 II 受体阻滞剂缬沙坦通过抑制糖尿病肾病小鼠的 miR-21 表达部分改善心脏纤维化
DOI:10.1016/j.mce.2017.12.005
发表时间:2018-09-05
期刊:MOLECULAR AND CELLULAR ENDOCRINOLOGY
影响因子:4.1
作者:Wang,Jinyang;Duan,Lijun;Wang,Shaocheng
通讯作者:Wang,Shaocheng
Metformin ameliorates skeletal muscle insulin resistance by inhibiting miR-21 expression in a high-fat dietary rat model.
二甲双胍通过抑制高脂饮食大鼠模型中的 miR-21 表达改善骨骼肌胰岛素抵抗
DOI:10.18632/oncotarget.20442
发表时间:2017-11-17
期刊:Oncotarget
影响因子:--
作者:Wang J;Gao Y;Duan L;Wei S;Liu J;Tian L;Quan J;Zhang Q;Liu J;Yang J
通讯作者:Yang J
SGLT2通过调控PI3K/Akt/mTOR信号通路在糖尿病心肌纤维化中的作用及机制研究
  • 批准号:
    82360163
  • 项目类别:
    地区科学基金项目
  • 资助金额:
    32万元
  • 批准年份:
    2023
  • 负责人:
    王金羊
  • 依托单位:
miR-21通过TGF-β/Smads对糖尿病心肌纤维化发病机制的影响及干预研究
  • 批准号:
    81560143
  • 项目类别:
    地区科学基金项目
  • 资助金额:
    39.0万元
  • 批准年份:
    2015
  • 负责人:
    王金羊
  • 依托单位:
国内基金
海外基金